Discovery of the Biosynthetic Machinery for Stravidins, Biotin Antimetabolites.
Discovery of the Biosynthetic Machinery for Stravidins, Biotin Antimetabolites.
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斯特拉维素、生物素抗代谢物生物合成机制的发现。
DOI：
10.1021/acschembio.9b00890
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发表时间：
2020
影响因子：
4
通讯作者：
Kelleher,NeilL
中科院分区：
文献类型：
--
作者：
Montaser,Rana;Kelleher,NeilL
Stravidins are peptide antibiotics produced byStreptomycesspp. Their antibacterial activity derives from an unusual amiclenomycin monomer, the warhead that inhibits biotin biosynthesis. Despite being discovered over five decades ago, stravidin biosynthesis has remained a mystery. Using our “metabologenomics” platform, we discover new stravidin analogues and identify the novel biosynthetic machinery responsible for their production. Analysis of the newly identified biosynthetic gene cluster (BGC) indicates the unusual amiclenomycin warhead is derived from chorismic acid, with initial steps similar to those involved inp-amino phenylalanine biosynthesis. However, a distinctive decarboxylation retains the nonaromatic character of a key ring and precedes a one-carbon extension to afford the warhead in its bioactive, untriggered state. Strikingly, we also identified two streptavidin genes flanking the new stravidin BGC reported here. This aligns with the known synergistic activity between the biotin-binding activity of streptavidin and the stravidins to antagonize both biotin biogenesis and bacterial growth.
